Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery

BACKGROUND: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach. METHODS: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores. RESULTS: We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62-74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3-4), forced expiratory volume in 1 s % predicted 49 (35-63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI -1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403). DISCUSSION AND CONCLUSION: A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful. TRIAL REGISTRATION NUMBER: NCT04034212

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK

INTRODUCTION: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS. METHODS AND ANALYSIS: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0-6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur. ETHICS AND DISSEMINATION: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBERS: NCT03387670; ISRCTN82598726

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS. Methods and analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0–6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years. Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate. The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression. Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur. Ethics and dissemination: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration numbers: NCT03387670; ISRCTN82598726

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction

Rationale: Exercise induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. Objectives: To evaluate exercise related changes in laryngeal aperture on ventilation, pulmonary mechanics and respiratory neural drive. Methods: We prospectively evaluated 12 subjects (six with EILO and six healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video, gastric-, esophageal- and transdiaphragmatic pressures, diaphragm electromyography and respiratory airflow. Results: The EILO and control groups had similar peak work rates and minute ventilation (V̇E) (work rate: 227±35 vs. 237±35W; V̇E: 103±20 vs. 98±23 L/min; p>0.05). At submaximal work rates (140-240W) subjects with EILO demonstrated increased work of breathing (p<0.05) and respiratory neural drive (p<0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure (p<0.05). Unexpectedly, a ventilatory increase (p<0.05), driven by augmented tidal volume (p<0.05), was seen in subjects with EILO, before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Conclusion: Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation

British Thoracic Society Clinical Statement on pulmonary rehabilitation

The evidence-based British Thoracic Society (BTS) Guideline for pulmonary rehabilitation (PR) in adults was published in 2013.(1) There is a strong evidence base for the benefits of PR,(2) and it is one of the most cost-effective interventions for adults with chronic obstructive pulmonary disease (COPD).(3) Furthermore, PR improves exercise capacity and health related quality of life (HRQOL) in COPD to a much greater magnitude than observed with bronchodilator therapy.(4)Since the guideline, there is deeper understanding of referral characteristics, outcome measures, patient selection, programme delivery, potential adjuncts, and the role of maintenance following PR. The BTS Clinical Statement on PR is a narrative review which provides a snapshot of current knowledge and best practice in topical areas by providing a series of clinical practice points that are informed by evidence where this exists, or based on expert opinion and collective clinical experience where evidence is limited.The Clinical Statement is not intended to be a comprehensive review as much of the BTS Guideline remains relevant today and does not need re-visiting.(1) Furthermore, the BTS, alongside other respiratory societies, reviewed the current state of education in PR.(5) The intended audience are PR clinicians working within health settings in the United Kingdom and beyond. The Clinical Statement will provide a framework to inform future BTS Quality Standards for PR. We have also highlighted areas of research priority, which will be of interest to clinical researchers.In this statement, we highlight the growing interest in alternative models of delivering PR (e.g. home-based, remote supervision, use of technology), accelerated by the restrictions placed on face-to-face PR delivery during the global COVID-19 pandemic. These PR models, typically delivered remotely, might potentially increase provision of, and accessibility to PR. However research gaps remain and it is crucial these models are optimised and carefully evaluated before widespread adoption.(2).A recent international workshop report, using a Delphi process, defined essential and desirable components of PR.(6) We have adapted this to define the core components of PR (Table 1), which will help health payers decide if they are commissioning an intervention that is likely to produce good outcomes

Diagnosis, medication, and surgical management for patients with trigeminal neuralgia: a qualitative study

BackgroundTrigeminal neuralgia (TN) is a serious health problem, causing brief, recurrent episodes of stabbing or burning facial pain, which patients describe as feeling like an electric shock. The consequences of living with the condition are severe. There is currently no cure for TN and management of the condition can be complex, often delayed by misdiagnosis. Patients’ qualitative experiential accounts of TN have not been reported in the literature. Capturing subjective experiences can be used to inform the impact of the condition on quality of life and may contribute to a better understanding of current clinical practice with the aim of improving patient care.MethodsParticipants with TN (n = 16; 11 female), including those who have and have not undergone surgical intervention(s), took part in one of four focus groups. We conducted a thematic analysis within an essentialist framework using transcripts.ResultsThe impact of TN and treatment on the lives of participants emerged as four predominant themes: (1) diagnosis and support with TN, (2) living in fear of TN pain, (3) isolation and social withdrawal, and (4) medication burden and looking for a cure. Each theme is discussed and illustrated with extracts from the transcripts.ConclusionsKey issues to address in the management of patients with TN include continued delays in diagnosis, persistent side effects from medication, and a lack of psychological support. Developing strategies to enhance the management of patients with TN, informed by a biopsychosocial approach and multidisciplinary team working, is essential to enhancing the provision of current care

Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study

Rationale: dietary nitrate supplementation improves skeletal muscle oxygen utilisation and vascular endothelial function. We hypothesised that these effects might be sufficient to improve exercise performance in patients with COPD and hypoxia severe enough to require supplemental oxygen.Methods: we conducted a single-centre, double-blind, placebo-controlled, cross-over study, enrolling adults with COPD who were established users of long-term oxygen therapy. Participants performed an endurance shuttle walk test, using their prescribed oxygen, 3 hours after consuming either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate) or placebo (nitrate-depleted BRJ). Treatment order was allocated (1:1) by computer-generated block randomisation.Measurements: the primary outcome was endurance shuttle walk test time. The secondary outcomes included area under the curve to isotime for fingertip oxygen saturation and heart rate parameters during the test, blood pressure, and endothelial function assessed using flow-mediated dilatation. Plasma nitrate and nitrite levels as well as FENO were also measured.Main results: 20 participants were recruited and all completed the study. Nitrate-rich BRJ supplementation prolonged exercise endurance time in all participants as compared with placebo: median (IQR) 194.6 (147.5-411.7) s vs 159.1 (121.9-298.5) s, estimated treatment effect 62 (33-106) s (p&lt;0.0001). Supplementation also improved endothelial function: NR-BRJ group +4.1% (-1.1% to 14.8%) vs placebo BRJ group -5.0% (-10.6% to -0.6%) (p=0.0003).Conclusion: acute dietary nitrate supplementation increases exercise endurance in patients with COPD who require supplemental oxygen.Trial registration number ISRCTN14888729.</p